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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： Antonio Masone Chiara Zucchelli enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

Genetic signatures of ERCC1 and ERCC2 expression, along with SNPs variants, unveil favorable prognosis in SCLC patients undergoing platinum-based chemotherapy

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Oncology research 2025年第1期33卷 45-55页

作者： enrico Caliman Sara Fancelli Federico Scolari Adriano Pasqui Clara Manneschi Daniele Lavacchi Francesca Mazzoni Francesca Gensini Valeria Pasini Camilla Eva Comin Luca Voltolini Serena Pillozzi Lorenzo Antonuzzo Clinical Oncology Unit Careggi University Hospital Florence 50134 Italy. Department of Experimental and Clinical Medicine University of Florence Florence 50134 Italy. Department of Health Sciences University of Florence Florence 50134 Italy. Medical Oncology Unit Careggi University Hospital Florence 50134 Italy. Department of Experimental and Clinical Biomedical Sciences "mario Serio" University of Florence Florence 50134 Italy. Section of Anatomic Pathology Department of Health Sciences University of Florence Florence 50139 Italy. Section of Surgery Histopathology and Molecular Pathology University of Florence Florence 50139 Italy. Thoracic Surgery Unit Careggi University Hospital Florence 50134 Italy.

Background:Platinum chemotherapy (CT) remains the backbone of systemic therapy for patients with small-cell lung cancer (SCLC). The nucleotide excision repair (NER) pathway plays a central role in the repair of the DNA damage exerted by platinum agents. Alteration in this repair mechanism may affect patients' survival.Materials and Methods:We conducted a retrospective analysis of data from 38 patients with extensive disease (ED)-SCLC who underwent platinum-CT at the Clinical Oncology Unit, Careggi University Hospital, Florence (Italy), from 2015 to 2020. mRNA expression analysis and single nucleotide polymorphism (SNP) characterization of three NER pathway genes-namely , , and -were performed on patient tumor samples.Results:Overall, elevated expression of genes was observed in SCLC patients compared to healthy controls. Patients with low and expression levels exhibited a better median progression-free survival (mPFS = 7.1 . 4.9 months, = 0.39 for and mPFS = 6.9 . 4.8 months, = 0.093 for ) and overall survival (mOS = 8.7 . 6.0 months, = 0.4 for and mOS = 7.2 . 6.2 months, = 0.13 for ). Genotyping analysis of five SNPs of genes showed a longer survival in patients harboring the wild-type genotype or the heterozygous variant of the rs11615 SNP ( = 0.24 for PFS and = 0.14 for OS) and of the rs13181 and rs1799793 SNPs ( = 0.43 and = 0.26 for PFS and = 0.21 and = 0.16 for OS, respectively) compared to patients with homozygous mutant genotypes.Conclusions:The comprehensive analysis of gene expression and SNP variants appears to identify patients who derive greater survival benefits from platinum-CT.

关键词： ERCC genes Nucleotide excision repair (NER) pathway Platinum-chemotherapy (CT) Single nucleotide polymorphisms (SNPs) Small cell lung cancer (SCLC)

How the optical timing system,the longitudinal diagnostics and the associated feedback systems provide femtosecond stable operation at the FERMI free electron laser

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High Power Laser Science and Engineering 2016年第2期4卷 14-28页

作者： mario Ferianis enrico Allaria Eugenio Ferrari Giulio Gaio Giuseppe Penco Fabio Rossi Marco Veronese Elettra-Sincrotrone Trieste S.C.p.A.

FERMI, the seeded free electron laser(FEL) in operation in Italy, is providing the User Community with unique fully coherent radiation, in the wavelength range 100–4 nm. FERMI is the first FEL fully synchronized by means of optical fibers. The optical timing system ensures an ultra-stable phase reference to its distributed clients. Several femtosecond longitudinal diagnostics verify the achieved performance; the bunch length monitor(BLM) and the bunch arrival monitor(BAM) will be presented in this paper. Feedback systems play a crucial role to guarantee the needed longterm electron beam stability. A real-time infrastructure allows shot-to-shot communication between front-end computers and the servers. Orbit feedbacks are useful in machine tuning, whereas longitudinal feedbacks control electron energy,compression and arrival time. A flexible software framework allows a rapid implementation of heterogeneous multiinput–multi-output(MIMO) longitudinal loops simply by selecting the appropriate sensors and actuators.

关键词： feedback system femtosecond longitudinal diagnostics optical timing

Molecular and Physiological Analysis of Growth-Limiting Drought Stress in Brachypodium distachyon Leaves

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Molecular Plant 2013年第2期6卷 311-322页

作者： Wim Verelst Edoardo Bertolini Stefanie De Bodt Klaas Vandepoele Marlies Demeulenaere mario enrico pè Dirk Inzé Department of Plant Systems Biology vie Technologiepark 927 9052 Gent Belgium Department of Plant Biotechnology and Bioinformatics Ghent University Technologiepark 927 9052 Gent Belgium Present address: Rijk Zwaan Zaadteelt en Zaadhandel B.V. Eerste Kruisweg 9 4793 RS Fijnaart The Netherlands Scuola Superiore Sant'Anna Piazza Martiri della Liberta 33 56127 Pisa Italy

The drought-tolerant grass Brachypodium distachyon is an emerging model species for temperate grasses and cereal crops. To explore the usefulness of this species for drought studies, a reproducible in vivo drought assay was developed. Spontaneous soil drying led to a 45% reduction in leaf size, and this was mostly due to a decrease in cell expansion, whereas cell division remained largely unaffected by drought. To investigate the molecular basis of the observed leaf growth reduction, the third Brachypodium leaf was dissected in three zones, namely proliferation, expan- sion, and mature zones, and subjected to transcriptome analysis, based on a whole-genome tiling array. This approach allowed us to highlight that transcriptome profiles of different developmental leaf zones respond differently to drought. Several genes and functional processes involved in drought tolerance were identified. The transcriptome data suggest an increased energy availability in the proliferation zones, along with an up-regulation of sterol synthesis that may influ-ence membrane fluidity. This information may be used to improve the tolerance of temperate cereals to drought, which is undoubtedly one of the major environmental challenges faced by agriculture today and in the near future.

关键词： Brachypodium drought stress plant growth leaf.

Experimental rigs for testing components of advanced industrial applications

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Friction 2019年第1期7卷 59-73页

作者： enrico CIULLI Department of Civil and Industrial Engineering University of Pisa

This paper presents experimental rigs of the Research Centre for the Mechanics of Turbomachinery of the Department of Civil and Industrial Engineering of the University of Pisa. Most of them were designed and constructed to allow investigations of real machine components and to furnish more realistic results than basic tribological test rigs. Tilting pad journal bearings, as well as gears and complete gearboxes for advanced industrial applications, can be tested using the rigs described in the paper. A novel test rig with a power rating of approximately 1 MW allows investigations of the static and dynamic characteristics of high-performance tilting pad journal bearings for turbomachinery. A twin disc machine and closed loop gear test rig are used to investigate the different kinds of wear mechanisms occurring in gears. Functional and durability tests on planetary gearboxes for new turbo-fan engines could be performed using another novel large test rig. A circulating power configuration was adopted for most of the rigs so that only the power needed to cover the friction losses has to be supplied, while the circulating power can be more than 20 times higher. All the test rigs include very complex load applications and lubrication plants, as well as dedicated control and data acquisition systems. The rigs and related plants were designed and constructed through strong and fruitful collaborations between the university and some large and small–medium companies. Despite some limitations in the publication of the results as a result of the industrial sensitivity of the data, the synergy among these different actors was stimulating and fundamental for the realization of new advanced industrial applications.

关键词： experimental rigs tilting pad journal bearings twin disc machine gears gearboxes

Addressing the Role of microRNAs in Reprogramming Leaf Growth during Drought Stress in Brachypodium distachyon

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Molecular Plant 2013年第2期6卷 423-443页

作者： Edoardo Bertolini Wim Verelst David Stephen Horner Luca Gianfranceschi Viviana Piccolo Dirk Iné mario enrico Pè Erica Mica Institute of Life Sciences Scuola Superiore Sant'Anna Piazza Martiri della Libertà 33 56127 Pisa Italy Department of Plant Biotechnology and Bioinformatics Ghent University Technologiepark 927 9052 Ghent Belgium Department of Plant Systems Biology VIB Technologiepark 927 9052 Gtlent. Belgium Department of BioSciences University of Milan via Celoria 26 20133 Milan Italy

Plant responses to drought are regulated by complex genetic and epigenetic networks leading to rapid reprogramming of plant growth, miRNAs have been widely indicated as key players in the regulation of growth and development. The role of miRNAs in drought response was investigated in young leaves of Brachypodium dis- tachyon, a drought-tolerant monocot model species. Adopting an in vivo drought assay, shown to cause a dramatic reduction in leaf size, mostly due to reduced cell expansion, small RNA libraries were produced from proliferating and expanding leaf cells. Next-generation sequencing data were analyzed using an in-house bioinformatics pipeline allowing the identification of 66 annotated miRNA genes and 122 new high confidence predictions greatly expand- ing the number of known Brachypodium miRNAs. In addition, we identified four TAS3 loci and a large number of siRNA-producing loci that show characteristics suggesting that they may represent young miRNA genes. Most miR- NAs showed a high expression level, consistent with their involvement in early leaf development and cell identity. Proliferating and expanding leaf cells respond differently to drought treatment and differential expression analyses suggest novel evidence for an miRNA regulatory network controlling cell division in both normal and stressed condi-tions and demonstrate that drought trigger a genetic reprogramming of leaf growth in which miRNAs are deeply involved.

关键词： miRNAs drought Brachypodium leaf development.

Single-particle spectral function of the Hubbard chain:frustration induced

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Chinese Physics B 2009年第6期18卷 2475-2480页

作者：王竞 enrico Arrigoni Department of Physics Fudan University Institute of Theoretical Physics and Computational Physics Graz University of Technology

The one-electron spectral function of a frustrated Hubbard chain is computed by making use of the cluster perturbation theory. The spectral weight we found turns out to be strongly dependent on the frustrating next-nearest-neighbor hopping t′. A frustration induced pseudogap arises when the system evolves from a gapful Mott insulator to a gapless conductor for an intermediate value of the frustration parameter ｜t′｜. Furthermore, the opening of a pseudogap in the density of states already in the metallic side leads to a continuous opening of the true gap in the insulator. For the hole-doped case, the pseudogap is pinned at the Fermi energy, while the Mott gap is shifted in energy with increasing Hubbard interaction U. The separation of the pseudogap and Mort gap in the hole-doped system demonstrates the validity of the existence of a pseudogap.

关键词： cluster perturbation theory pseudogap metal-insulator transitions

Mortality from chronic liver disease:Recent trends and impact of the COVID-19 pandemic

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World Journal of Gastroenterology 2023年第26期29卷 4166-4173页

作者： Ugo Fedeli Claudio Barbiellini Amidei Veronica Casotto enrico Grande mario Saia Alberto Zanetto Francesco Paolo Russo Epidemiological Department Azienda ZeroVeneto RegionPadova 35132Italy Integrated System for Health Social Assistance and WelfareNational Institute of StatisticsRome 00184Italy Clinical Governance Azienda ZeroVeneto RegionPadova 35132Italy Department of Surgery Oncology and Gastroenterology University of PaduaPadova 35128Italy Gastroenterology and Multivisceral Transplant Unit Azienda Ospedale-Universitàdi PadovaPadova 25128Italy

Prepandemic time trends in mortality from chronic liver disease(CLD)differed according to specific cause of death(decreasing for liver cirrhosis,stable or increasing for liver cancer),etiology(increasing for nonalcoholic fatty liver disease,generally decreasing for other etiologies),and world region(decreasing in areas with the highest burden of hepatitis B virus,increasing in Eastern Europe and other countries).The coronavirus disease 2019(COVID-19)pandemic affected mortality of patients with CLD both directly,with a higher risk for severe illness and death depending on age,stage and etiology of the disease,and indirectly,through social isolation and loss of support,harmful drinking,and difficulties in access to ***,only sparse data are available on variations in CLD as a cause of death during the *** the USA,in 2020-2021 a growth in mortality was registered for all liver diseases,more marked for alcoholic liver disease,especially among young people aged 25-44 years and in selected ethnic ***-19 related deaths accounted only for a minor part of the *** data from mortality registers of other countries are warranted,preferably adopting the so-called multiple cause-of-death approach,and extended to deaths attributed to viral hepatitis and liver cancer.

关键词： Mortality Multiple causes of death COVID-19 Chronic liver disease Liver cirrhosis Liver cancer

Optimized design and integration of energy storage in Solar-Assisted Ground-Source Heat Pump systems

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Building Simulation 2023年第10期16卷 1933-1948页

作者： Maria Ferrara enrico Fabrizio Department of Energy Politecnico di TorinoTurin10121Italy

The integrated use of multiple renewable energy sources to increase the efficiency of heat pump systems,such as in Solar Assisted Geothermal Heat Pumps(SAGHP),may lead to significant benefits in terms of increased efficiency and overall system performance especially in extreme climate contexts,but requires careful integrated optimization of the different system *** particular,thermal storages take a fundamental role in optimizing the integration of renewable energy sources and the system *** work investigates the potential design optimization of a SAGHP system in a mountain site by exploring many different alternatives to optimize the mutual relationship between the solar field,the geothermal field and the water thermal *** is done through an original simulation-based multi-objective optimization framework considering energy efficiency and economic feasibility,which allows appraising the impact of the different design alternatives on the overall system performance and on the dynamics of the different system *** identify a set of optimized system configurations that optimize the integrated exploitation of the different thermal sources showing a potential increase of the overall system performance leading to 34%lower global cost compared to the initial *** robustness of the optimal design solutions is reported with respect to the current context of high economic uncertainty.

关键词： thermal storage geothermal energy heat pumps building simulation artificial intelligence cost optimization energy flexibility